1-Bromo-4-fluorobenzene → 8-[2-(4-Fluoro-phenyl)-2-hydroxy-cyclohexyl]-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one

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Reaction Steps

To a solution of 1-bromo-4-fluorobenzene (1.4 g, 8 mmol) in dry THF (5 mL) under argon at −78° C. was added BuLi (1.6 M in hexanes, 5 mL, 8 mmol) and the mixture maintained at this temperature for 1 h. To this solution was added a solution of 8-(2-oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one (687 mg, 2 mmol) in dry THF (15 mL) and the reaction mixture allowed to warm up to −20° C. after 2 h before ammonium chloride (saturated, 20 mL) was added. The resulting mixture was then evaporated and water (20 mL) added. The product was extracted with ethyl acetate (3×15 mL) and the combined organic extracts washed with brine (10 mL), dried over sodium sulfate, filtered and evaporated to leave a light brown solid. Purification by chromatography on silica gel eluting with DCM:MeOH—NH4OH (0.5%) (95:5 to 4:1) afforded the title compound (380 mg, 45%) which was obtained as a white solid. MS: m/e=423.5 (M+H).

Provenance & Evidence